Naslov
Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies

Autori
Šimić, Goran ; Babić Leko, Mirjana ; Wray, Selina ; Harrington, Charles ; Delalle, Ivana ; Jovanov-Milošević, Nataša ; Bažadona, Danira ; Buée, Luc ; de Silva, Rohan ; Di Giovanni, Giuseppe ; Wischik, Claude ; Hof, Patrick R.

Izvornik
Biomolecules (2218-273X) 6 (2016), 1; 6, 28

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Alzheimer’s disease ; amyloid ; neurofibrillary degeneration ; microtubules ; neuropathology ; phosphorylation ; protein aggregation ; protein oligomerization ; tauopathies ; tau protein

Sažetak
Abnormal deposition of misprocessed and aggregated proteins is a common final pathway of most neurodegenerative diseases, including Alzheimer’s disease (AD). AD is characterized by the extraneuronal deposition of the amyloid beta protein in the form of plaques and the intraneuronal aggregation of the microtubule-associated protein tau in the form of filaments. Based on the biochemically diverse range of pathological tau proteins, a number of approaches have been proposed to develop new potential therapeutics. Here we discuss some of the most promising ones: inhibition of tau phosphorylation, proteolysis and aggregation, promotion of intra- and extracellular tau clearance, and stabilization of microtubules. We also emphasize the need to achieve a full understanding of the biological roles and post-translational modifications of normal tau, as well as the molecular events responsible for selective neuronal vulnerability to tau pathology and its propagation. It is concluded that answering key questions on the relationship between amyloid beta and tau pathology should lead to a better understanding of the nature of secondary tauopathies, especially AD, and open new therapeutic targets and strategies.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija

POVEZANOST RADA